title: Telomerase and primary T cells: biology and immortalization for adoptive immunotherapy.
abstract: Telomeres are specialized repeats, present at the end of chromosomes, whose loss during cell division is followed by growth arrest, a central mechanism of replicative senescence in human cells. Telomere length in stem cells is maintained by telomerase, a specialized reverse transcriptase, whose function is to restore shortening telomeres. Unlike most somatic cell types, human T lymphocytes are capable of briefly reactivating telomerase expression at the time of stimulation. Telomerase expression in T lymphocytes is modulated by a variety of external stimuli and by viral infections. However, telomerase reactivation in stimulated, proliferating human T lymphocytes is limited and cannot prevent the ultimate onset of senescence. Ectopic telomerase expression can rescue human and macaque antigen-specific T cells from senescence. Primary T cells have been engineered with telomerase to have substantially extended replicative lifespans without the loss of primary cell functions or malignant transformation. 'Immortal' antigen-specific T-cell lines and clones overexpressing telomerase are an invaluable source of well-characterized quasi-primary T cells for research of T-cell biology and are potentially useful for immunotherapy of cancer and AIDS.
authors.affiliation: SAIC-Frederick, Inc., National Cancer Institute-Frederick, Frederick, MD 21702, USA. eugene.barsov@nih.gov
authors.forename: Eugene V
authors.initials: EV
authors.lastname: Barsov
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002455:Cell Division; D002470:Cell Survival / Q000235:genetics*; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics; D002875:Chromosomes / Q000378:metabolism; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008251:Macaca; D012091:Repetitive Sequences, Nucleic Acid; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology / Q000378:metabolism; D019098:Telomerase / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D016615:Telomere / Q000378:metabolism; D014170:Transformation, Genetic
chemical_list: C509186:TERT protein, human; D019098:Telomerase